原发性肥厚性骨关节病(PHO)是一种遗传性疾病,以数字棍棒为特征,骨膜增生,和厚皮症.基于两个致病基因,羟基前列腺素脱氢酶(HPGD)和溶质载体有机阴离子转运蛋白家族成员2A1(SLCO2A1),PHO分为两种亚型:肥厚性骨关节病,小学,常染色体隐性遗传1(PHOAR1)和肥厚性骨关节病,小学,常染色体隐性遗传2(PHOAR2)。在这项研究中,我们总结了23例PHOAR2患者的临床表现并分析了SLCO2A1基因。因此,18例患者显示完整的PHO表型与数字俱乐部,骨膜增生,和厚皮症.总共发现了29个突变,其中22个是新的突变,包括13个错义,三个废话,四个删除,一个移码和一个剪接位点突变。与我们之前报道的9例PHOAR1患者相比,具有SLCO2A1突变的PHO患者均为男性,发病年龄较晚。消化性溃疡和骨髓纤维化仅发生在PHOAR2患者中。PHOAR2组患者尿中前列腺素E2代谢物(PGEM)水平明显高于PHOAR1组。总之,这项研究是迄今为止最大的队列,用于总结PHOAR2患者,并评估PHO两种亚型之间的表型差异.两种亚型之间的尿PGEM浓度差异有助于PHO的鉴别诊断。
Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis, and pachydermia. Based on two causative genes, hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), PHO is categorized into two subtypes: hypertrophic osteoarthropathy, primary, autosomal recessive 1 (PHOAR1) and hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2). In this
study, we summarized the clinical manifestations and analyzed SLCO2A1 gene in 23 PHOAR2 patients in our center. As a result, 18 patients displayed complete phenotypes of PHO with digital clubbing, periostosis, and pachydermia. 29 mutations were found in total, and 22 of them were novel mutations including 13 missense, three nonsense, four deletion, one frame-shift and one splicing site mutations. Compared with nine PHOAR1 patients we previously reported, PHO patients with SLCO2A1 mutations were all male and presented with a later onset age. Peptic ulcers and myelofibrosis occurred only in PHOAR2 patients. The urinary level of prostaglandin E2 metabolite (PGEM) is significantly higher in PHOAR2 patients than that in PHOAR1 group. In conclusion, this
study was the largest cohort to date to summarize PHOAR2 patients and to assess the phenotypic difference between two subtypes of PHO. The difference of urinary PGEM concentration between two subtypes is helpful for the differential diagnosis of PHO.